Ideas about the importance of knowledge and innovation in the global economy have implications for the changing role of universities but so too do ideas about the role of place-based knowledge in generating competitive advantage and innovation at the regional scale. As the concern to structure effective innovation systems intersects with the growing interest in distinctive, place-based knowledge, an opportunity emerges to reconsider the role of universities in regions. As institutions specialized in knowledge creation and knowledge transfer, regional university campuses are in a key position to catalyze regional development outcomes by bringing together different forms of knowledge, including place-based knowledge, in new ways. In line with current thinking about open and user-generated innovation, it is arguable that this kind of approach to co-creating knowledge in place can catalyze regional development outcomes. Yet for university campuses to take on this catalyst role, they must move beyond the limitations of their current "engagement" approaches. This paper explores some of the limitations and conflicts in current regional engagement approaches, then considers how the meeting-point between universities and complex regions may be operationalized in practice.